Understanding the pathogenesis of allergic asthma using mouse models

Objective: This paper reviews the current views of the pathogenesis of airw ay eosinophilic inflammation and airway hyperresponsiveness (AHR) in allerg ic asthma based on mouse models of the disease. The reader will also encoun ter new treatment strategies that have arisen as this knowledge is applied in practice. Data sources: MEDLINE searches were conducted with key words asthma, mouse model, and murine. Additional articles were identified from references in a rticles and book chapters. Study selection: Original research papers and review articles from peer-rev iewed journals were chosen. Results: Although the mouse model does not replicate human asthma exactly, the lessons learned about the pathogenesis of allergic airway inflammation and AHR are generally applicable in humans. Type 2 T helper lymphocytes (Th 2) orchestrate the inflammation and are crucial for the development of AHR. Cells and molecules involved in T cell activation (dendritic cells, T cell receptor, major histocompatibility complex molecule. and costimulatory mol ecules) are also vital. Besides these, no other cell or molecule could be s hown to be indispensable for the establishment of the model under all exper imental conditions. There are at least three pathways that lead to AHR. One is dependent on immunoglobulin E and mast cells. one on eosinophils and in terleukin-5 (IL-5), and one on IL-13. Eosinophils are probably the most imp ortant effector cells of AHR. Radical methods to treat asthma have been tes ted in the animal model. including modifying the polarity of lymphocyte res ponse and antagonizing IL-5. Conclusions: AHR. the hallmark of asthma, is attributable to airway inflamm ation ultimately mediated by helper T cells via three pathways, at least. T he mouse model is also a valuable testing ground for new therapies of asthm a.